Mercaptoethylation of amines with carbamates



United States Patent man Kodak Company, Rochester, N.Y.,. a corporationof New Jersey No Drawing. Original application Apr. 26, 1961, Ser. No.105,568. Divided and this application Jan. 4, 1965, Ser. No. 423,341

6 Claims. (Cl. 260-2471) This application is a division of the'U.S.patent application of Delbert D. Reynolds, Serial No. 105,568, filedApril 26, 1961, for'Mercaptoethylat-ion of Amines With EthyleneMonothiolcarbonate and Z-Mercaptoethylcarbonates which was acontinuation-in-part of and copending with application Serial No.721,678, filed March 17, 1958, now abandoned, said application SerialNo. 721,678 having been continuation-in-part of and copending withapplication Serial No. 647,499, filed March 21, 1957, now U.S. Patent2,828,318.

This invention concerns a process for introducing the mercaptoethyl,radical into amines, more. particularly mercaptoethylating amines, andpreparing 2-mercaptoethyl carbamates.

Mercaptans and their derivates are required for use in manyapplications, particularly for use in the rubber industry, as disclosedby H. R. Snyder et al., J. Amer. Chem. Soc, 69, 2672 (1947). They arealso useful in the pharmaceutical field as disclosed by R. 0. Clinton etal., J. Amer. Chem. Soc, 70, 950 (1948), and in the photographicindustry in photographic emulsions and the like.

One broad class of useful mercaptan derivatives is the mercaptoethylderivatives, in particular those derived from amines and having thegeneral formula RR'NCH CH SH, where R and R are hydrogen, alkyl, aryl oraralkyl. Three methods have customarily been used to synthesize thesecompounds. One involves the reaction of aminoethyl halides withhydrosulfides of the alkali metals. Another is based on the condensationof aminoethyl halides with thiourea followed by alkaline hydrolysis. Athird and more preferred method is the mercaptoethylation of primary andsecondary amines by reaction with ethylene sulfide. This process leavesmuch to be desired because of the difiiculties encountered in handlingethylene sulfide. Ethylene sulfide readily polymerizes and cannot bestored safely in large quantities. Hence this process is not suitablefor mercaptoethylation on a large scale.

In my U.S. Patent No. 2,828,318, which issued March 25, 1958, a processis disclosed for preparing ethylene sulfide which involves the thermaldecomposition of ethylene monothiolcarbonate according to the followingequation:

The ethylene monothiolcarbonate is a high-boiling liquid which is stableunder normal conditions and therefore, unlike ethylene sulfide, it canbe kept for extended periods of time. Like ethylene sulfide, however, itreacts with primary or secondary amines to yield mercapto derivatives.

One object of this invention is to obtain mercaptoethyl derivatives bythe mercaptoethylation of primary or secondary amines. Another object isto provide a mercaptoethylatio-n process which avoids the diflicultiesinherent in using ethylene sulfide due to its inclination forpolymerization. An additional object is to obtain mercaptoethylderivatives.

The invention is illustrated by the reaction in which ethylenemonothiolcarbonate is treated. with greater than one mole of a typicalamine to. yield an aminoethanethiol and carbon dioxide. This reactioncan be called mercaptoethylation of an amine.

Ethylene monothiolcarbonate may be reacted with one.

mole or less of any primary or secondary amine which may be aliphatic orcyclic to form carbamates. Any amine with a replaceable hydrogen atom isoperative in this process including diamines. The resulting product hasa general formula of G[CO CH CH SH] or of G[CO CH CH S(Q)]- in which nis 1 or 2, and G and Q are defined herein. The preparation of thesecarbamates is preferably carried out at 0, to 25 C.

Primary and secondary mercaptoethylamines which are aliphatic, aromatic,or cyclic may be prepared by reacting the amines with B[CO CH CH S(Q)](i.e., mercaptoethylating amines using Z-mercaptoethyl carbamates) whereB is G, anilino, alkyl or alkoxy (C -C ring-substituted anilino,halogen-substituted anilino, and phenyl-' enediamino. When B is isderived from an aromatic amine, the B-[CO CH CH S(Q)] is obtainable fromreacting t-he corresponding isocyanate or diisocyanate with HOCH CHS(Q), and a basic catalyst is required in its subsequent use as amercaptoethylating agent.

The process may be carried out by mercaptoethylating primary andsecondary amines which are aliphatic, aromatic, or cyclic amines byreacting ethylene monothiolcarbonate with greater than one mole ofamines.

When pure, ethylene monothiolcarbonate is stable at reflux temperature(237 C.). However, in the presence of a base, including amines, itdecomposes to yield ethylene sulfide and CO However, an alkalinecatalyst such as sodium methoxide is required to decompose the ethyl,-ene monothiolcarbonate when the amine reactant is aromatic. The ethylenesulfide then reacts with the amine to form a mercaptoethylamine.

In general, any amino function in the presence of other nonparticipatingfunction, for example, polyamines, polyimines, amino acids,polypeptides, proteins, amino sugars, deacetylated chitin, gelatin, andthe like can be mercaptoethylated.

Using the process of reacting ethylene monothiolcarbonate with one moleor less of an amine, new carbamates can be prepared which aremercaptoethylating agents of the formula:

G z Z Z (Q) in in which the Q may be H, COR, CO R, COG and C(NH)NH -HXin which X may be chloride or bromide; and n may be 1 or 2. When n is 1,G may be RHN, RRN, and ZN-, where R is alkyl (C -C or cycloalkyl and Zmay be 4 or 5 atoms necessary to complete a heterocyclic ring with N.The atoms may be all carbon atoms or an oxygen or nitrogen atom combinedwith three or more carbon atoms. When n' is 2, G may be where Y ishydrogen or R (defined above) and x is 2 to 18.

The following examples are intended to illustrate my invention but arenot intended to limit it in any way.

EXAMPLE 1 Ethylene monothiolcarbonate A mixture of 760 g. (5.0 moles) ofethyl 2-hydroxyethylthiolcarbonate, B.P. 108 C./5 mm., 11 1.4782,

3 190.5 g. (1.0 mole) of p-toluenesulfonic acid monohydrate and 1.5 l.of benzene was refluxed for 4 hours under an 18" glass-helices packeddistillation apparatus. During this period the benzene-water-alcohol andthen the henzene-alcohol azeotropes were continuously distilled at arate to maintain a stillhead temperature of 70 C.

The reaction mixture was cooled and the polymer formed during thereaction further precipitated by the addition, with stirring, of 1.5 l.of ether. After filtering off the polymer, the acidic filtrate wasneutralized with an aqueous sodium carbonate solution (62.0 g., 0.05mole, of sodium carbonate in 500 ml. of water) and the pH adjusted toabout 6 by the addition of 10 ml. of glacial acetic acid. The organiclayer was separated, stabilized with 20.0 g. of stearic acid, anddistilled under reduced pressure through an 18" glass-helices packedcolumn to yield 384 g. (73.6 percent) of product, B.P. 75/1.0 mm. n1.5104. To prevent possible contamination of product duringdistillation, it was found necessary to remove a small amount of whitecrystalline material identified as 1,4-dithiane (M.P. 105, calcd.: C,40.0; H, 6.7. Found: C, 39.5; H, 6.5) from the cold finger just prior tothe distillation of the ethylene monothiolcarbonate.

EXAMPLE 2 2-diethylamin0ethanethiol One mole (73 g.) of diethylamine wasrefluxed with 150 ml. of anhydrous toluene. One-half mole (52 g.) ofethylene monothiolcarbonate was added through a dropping funnel and therefluxing continued for sixteen hours. The toluene was removed underreduced pressure, and the reaction products distilled at 8385 at 57 mm.through a 10" x 1" glass column packed with glass helices, and equippedwith a variable-take-off still head. Forty-one and five-tenths g. (62.4percent) of Z-diethylaminoethanethiol were collected, n =1.4650.Redistillation of 8485 at 55 mm. gave n =1.4632.

Analysis.Calcd. for C H NS: C, 54.1; H, 11.3; N, 10.5; S, 24.1. Found:C, 54.1; H, 11.3; N, 10.3; S, 23.9.

A higher boiling fraction (7.5 g.) B.P. 85-150 at 57 mm. was obtainedfrom this first distillation. A high sulfur and low carbon also lownitrogen content indicates it is composed of high mercaptoethylationproducts.

EXAMPLE 3 2-di-n-butylaminoethanethiol One mole (129 g.) ofdi-n-butylamine was refluxed in 150 ml. of anhydrous dioxane. One-halfmole of ethylene monothiolcarbonate was added and the refluxingcontinued for 15.5 hours. The dioxane was removed under reduced pressureand 200 ml. of toluene added. After washing the toluene with cold water,the excess dibutyl-' amine and toluene were distilled at reducedpressure. 2- di-n-butylaminoethanethiol was then distilled. Yield 60 g.(63%); B.P. 60 at 0.3 mm., n =1.4620.

Analysis.Calcd. for C H NS: C, 63.5; H, 12.1; N, 7.4; S, 16.9. Found: C,63.6; H, 12.1; N, 7.6; S, 16.9.

EXAMPLE 4 2-piperidinoethanethiol One mole of piperidine (85 g.) wasrefluxed in 150 ml. of anhydroustoluene. One-half mole of ethylenemonothiolcarbonate was added and the refluxing continued for seventeenhours. The toluene and excess piperidine were distilled at atmosphericpressure through a 12" glass packed column. The undistilled productcontained some piperidine carbonate. After cooling, it was mixed with400 ml. of ether and washed with 100 m1. of cold water. After dryingover MgSO the ether was distilled. The Z-piperidinoethanethiOl (51 g.)distilled at 84 at 14 mm. n =1.4989. Yield 70%.

4 Analysis.--Calcd. for C H NS: C, 58.0; H, 10.3; N, 9.7; S, 22.0.Found: C, 57.9; H, 10.5; N, 9.7; S, 21.5.

EXAMPLE 5 2-m0rph0lin0ethanethi0l One mole of morpholine (87 g.) wasrefluxed in 150 ml. anhydrous toluene. After adding 52 g. (0.5 mole) ofethylene monothiolcarbonate the solution was refluxed for seven hours.After cooling, the solution was washed with cold water to removemorpholine carbonate. Distillation yielded 42 g. ofZ-morpholinoethanethiol (57%) 12 1.5022.

Arzalysis.-Calcd. for C H NOS: C, 48.9; H, 8.8; N, 9.5; S, 21.8. Found:C, 48.8; H, 8.7; N, 9.0; S, 21.7.

EXAMPLE 6 2-benzylamin0ethanethiol EXAMPLE 7Di-n-butylaminoethylmercaptoethanethiol A mixture of 60 g. ofdi-n-butylaminoethanethiol (0.32 mole), from Example 3, ml. of anhydroustoluene, and 34 g. of ethylene monothiolcarbonate was refluxed forseventeen hours. The reaction mixture was washed with 200 ml. of waterand dried over MgSO After removal of the toluene, the product wasfractionated.

Fraction Amount, g. B.P.

Fraction 3 represents a 45% yield.

Analysis.-Calcd. for C H NS C, 57.8; H, 10.8; N, 5.6; S, 25.7. Found: C,57.9; H, 10.6; N, 5.6; S, 25.6.

EXAMPLE 8 Since many amines have low-boiling points, very low reactiontemperatures are obtained at normal pressure. With aromatic amines abasic catalyst, such as sodium methoxide, is used. By conducting thereaction in a rocking-type autoclave, employing a positive displacementpump to meter the ethylene monothiolcarbonate into the amine-solventmixture, yields can be significantly improved. A 7 percent yield of2-isopropylaminoethanethiol was obtained by employing a reactiontemperature of about 50 C. at atmospheric pressure.

A 77 percent yield was obtained of 2-isopropylaminoethanethiol byconducting the reaction at C. for 15 minutes in an autoclave. Similarincreases in yields were obtained for a number of other low-molecularweight amines, which are marked with an asterisk in Tables I and II,following Example 9. In each instance, the pressure was that generatedby the reaction.

EXAMPLE 9 Ethylene monothiolcarbonate was refluxed with a series ofamines using a twofold molar excess of the amines, refluxing the amineswith the ethylene monothiolcarbonate in toluene overnight using aneflicient condenser. The resulting 2-aminoethanethiols were isolated bydistillation. These are given in Tables I and II. The yields representeda substantial improvement over those The reaction mixture Found FoundAnalysis, percent 2CH2SH+ C O 2 Analysis, percent initially under waterpump vacuum to remove solvent and unreacted starting materials, and thenby vacuum pump to yield analytically pure product. Due to its highboiling point, distillation of the carbamate from ben- Calculated TableIII) was effected through a 3 Calculated TABLEI I z RNHCHzOH2SH+CO2 Szylamine (No. 9, unpacked column.

(b) The biscarbamates of piperazine and ethylene diamine (Nos. and 11,Table III) were prepared by the same procedure as in (2.) except that0.25 mole of starting amine was used. Both biscarbamates crystallizedafter removal of solvent, and were recrystallized twice from ethanol.

TABLE II (DEF-CH O b ALP. lb-43 C.

obtained by direct reaction of an amine with ethylene sulfide, and theelimination of the isolation and handling of the sensitive ethylenesulfide allows this process to be used for large-scale use.

011 N --N N7-.

EMMPLE 10 Z-mercaptoethyl carbamates The mixture was then subjected todistillation,

" M.P. 3435 C.

(a) Carbamates 1-9, Table III, were prepared by allowing a mixture of0.55 mole of ethylene monothiolcarbonate, 0.5 mole of amine and 500 ml.of dioxane 14h--- HOCHzCH2NCH to stand at 25-30 C. for a reaction periodindicated in Table I.

TABLE III.2-MERCAPTOETHYL CA RBAMATES Percent yield for Analysis,percent reaction time (hrs) of-- G B IJmm 71,, Calculated Found 11. orM.P.

15 60 90 170 C H N S C H N S n-C II NII 1 80 98/0. 5 1. 4782 47. 5 8. 57. 9 18. 1 47. 4 8. 6 7. 9 18. 1 n-C H NII 1 83 134/0. 3 1. 4755 52. 79. 3 6. 8 15. 6 52. 7 8. 9 7. 2 15. 7 CH2:OHCH2NH 1 43 83/0. 2 1. 497844. 7 6. 8 8. 7 l9. 9 43.9 6. 9 8. 4 20. 1 (CI-1;);CHNLP- 1 10 93/1. l.4792 44. 2 8. 0 8. 6 19. 6 44. 6 8. 4 8. 8 19. 6 (n-C4H9)zN 1 O 106/0.6 1. 4660 56. 7 9. 9 6. 0 l3. 7 57. 2 10. 2 6. 2 14. O

6 O N 1 60 78 86 108/0. 6 1. 5058 44. 0 6. 8 7. 3 l6. 8 44. 2 6. 9 7. 016.

8 CH3N N 1 82 118/1.0 1.5078 47.1 7.8 13.7 15.7 46.8 8.1 13.6 15,5

9 O H CHgNH- 1 56 151/0. 05 1.5531 56.8 6.2 6.6 15.2 57.6 6.6 7.6 15.2

N N 2 86 u... 72-74 40.8 6.1 9.5 21.8 41.0 6.2 9.9 21.6

11 -HNCH2CH2NH----- 2 70 101-104 35.8 6.0 10.4 23.9 36.6 6.5 9.9 23.9

EXAMPLE 1 1 the silver image. Instead of this procedure the amino- Amixture of 0.5 mole of GCO CH CH SQ, 1.5 mole of morpholine, and 250 ml.of toluene were refluxed overnight under an efiicient condenser.Isolation of the product, 2-morpholinoethanethiol, was effected bydistillation under reduced pressure through a 14" Vigreux columnequipped with a variable take-off head. The yields of2-morpholinoethanethiol are listed in Table IV.

ethanethiols may be applied to the developed print in vapor form from aboiling aqueous solution with the result that a stable silver complex isformed. This procedure obviates the usual fixing and washing steps.However, the aminoethanethiols may be used in solutions for fixingprints in the usual manner, in which case they form soluble salts withthe residual silver halide which can be My process of mercaptoethylatingamines with ethylene monothiolearbonate has many advantages over systemsusing ethylene sulfide since my mercaptoethylating agent is stable andmay be stored under normal conditions. Good yields of mercaptoethylatedproducts are obtained without formation of polyethylene sulfide. Thisnew process of mercaptoethylating amines is to be preferred over thereactions involving Z-chloroethylamines because of the more readilyavailable starting materials.

The reactants can be dissolved in suitable inert common solvents, suchas toluene, dioxane, xylene and the like and heated to the refluxtemperature of the solvent used.

The aminoethanethiols of this invention may be used in photography forvarious purposes. For example, it is well known in photography to fixsilver halide emulsion layers subsequent to development in order tostabilize 1. The process which comprises contacting a stoichiometricexcess of an organic amine selected from the group consisting of:

(a) primary organic amines and 9 (b) secondary organic amines with acompound having the formula:

B 2 2 2 (Q) ln wherein n is an integer from 1 to 2; B, when n is 1, isselected from the group consisting of:

(b) -N O (c) -N N CHs and R is selected from the group consisting of:(a) hydrogen and R is selected from the group consisting of (a) alkyl of1 to 18 carbons; (in) allyl, (c) benzyl, (d) cyclohexyl, (e)cyclopentyl, (f) -CH CH OH, (a) p y (h) lower alkyl phenyl, (i) loweralkoxy phenyl, and (j) halogenated phenyl;

10 x is an integer from 2 to 18; and Q is selected from the groupconsisting of: (a) hydrogen .a 7 COZCGHB: (d) --C(=NH)NH -HCl, (e) CONHCH 2. The process which comprises contacting a compound of the formula:

with a stoichiometric excess of morpholine.

3. The process which comprises contacting a compound of the formula:

C H NHCO CH CH SH with a stoichiometric excess of morpholine.

4. The process which comprises contacting a compound having the formula:

with a stoichiornetric excess of morpholine.

5. The process which comprises contacting a compound of the formula:

with a stoichiornetric excess of morpholine.

6. The process which comprises contacting a compound of the formula:

n-C H NHCO CH CH SCO C H -n with a stoichiometric excess of morpholine.

No references cited.

NICHOLAS S. RIZZO, Primary Examiner.

1. THE PROCESS WHICH COMPRISES CONTACTING A STOICHIOMETRIC EXCESS OF ANORGANIC AMINE SELECTED FROM THE GROUP CONSISTING OF: (A) PRIMARY ORGANICAMINES AND (B) SECONDARY ORGANIC AMINES WITH A COMPOUND HAVING THEFORMULA:
 2. THE PROCESS WHICH COMPRISES CONTACTING A COMPOUND OF THEFORMULA: